A 58-year-old previously healthy man had complaints of fluctuating drooping eyelids and weakness of neck extensors, arms, and legs. He almost continuously experienced double vision. Following a diagnosis of myasthenia gravis and improvement with pyridostigmine, he noticed twitches and spasms of muscles virtually all over his body. This became severe, he did not sleep well, was restless, and almost continuously felt the urge to move and walk around. His wife mentioned that he also behaved differently. Initially, a pyridostigmine intoxication was considered, but lowering the dose did not help. Additionally, some autonomic features (constipation, erectile dysfunction) appeared.

The description of VGKC antibodies detected by radioimmunoassay (RIA) led to mischaracterizing as autoimmune an extensive number of syndromes in many patients who in fact did not have autoimmune disorders. We now know that VGKC antibodies demonstrated by RIA have no clinical value, unless the presence of LGI1 and CASPR2 antibodies are demonstrated by cell-based assays. Limbic encephalitis is by far the most frequent disorder associated with LGI1 antibodies. It usually occurs in the elderly (median age ~65 years) and ~65% are male. Anti-LGI1 encephalitis is frequently preceded by faciobrachial dystonic seizures that are very characteristic of this disorder and should prompt early-onset immunotherapy to prevent the development of memory and cognitive deficits. Most patients do not have cancer or other types of tumours, with the exception of thymoma in a few cases. Patients with CASPR2 antibodies may present with symptoms of encephalitis or peripheral nervous system hyperexcitability (neuromyotonia), and sometimes they develop Morvan syndrome. This disorder is characterized by a severe sleep dysfunction named agrypnia excitata, along with hallucinations, cognitive decline, dysautonomia, and neuromyotonia. Up to 50% of patients with Morvan syndrome have an underlying thymoma. As with other encephalitis associated with antibodies against neuronal surface antigens, patients with encephalitis associated with LGI1 and CASPR2 antibodies usually respond to immunotherapy.

This chapter focuses on several types of sleep disorders in patients with autoimmune encephalitis, including narcolepsy, REM sleep behaviour disorder (RBD), NREM sleep parasomnias, and central and obstructive sleep apnoeas. Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness and severe and irresistible episodes of daytime sleep. Narcolepsy is caused by a T cell-mediated destruction of hypocretin-synthetizing neurons located in the hypothalamus. Patients with anti-NMDAR encephalitis develop severe insomnia at disease onset, and many of them have hypersomnia after the acute stage of the disease or during clinical recovery. Patients with anti-LGI1 encephalitis frequently develop REM sleep behaviour disorder. Patients with Morvan syndrome and CASPR2 antibodies present a sleep disorder called agrypnia excitata that consists of severe insomnia, motor and sympathetic hyperactivity, quasi-purposeful movements, and enacted dreams in the setting of loss of slow-wave sleep and circadian rhythmicity. Sleep alterations occur in >80% of patients with anti-IgLON5 disease; the most characteristic are sleep apnoeas and non-REM and REM parasomnias. Symptoms of excessive daytime sleepiness, sometimes with findings suggestive of narcolepsy, were reported in about 30% of patients with paraneoplastic anti-Ma2 encephalitis, and less frequently in patients with neuromyelitis optica spectrum disorders associated with aquaporin 4 antibodies.